12-Month SUI Data, FDA OKs VIVEVE 2 To Progress, LIBERATE U.S. Start-Date Pushed Back
It has been a busy few weeks for Viveve (NASDAQ:VIVE). In addition to raising nearly $19M (net) via the sale of common shares, they recently announced compelling 12-month results from their n=36 SUI feasibility study and got the green light from FDA to forge ahead with VIVEVE II (their pivotal U.S. study in sexual function). Below we discuss these, as well as other updates on the ongoing clinical programs in both sexual function and SUI.
12-Month SUI Feasibility Study Data Further Supports Compelling Efficacy Signal…
Earlier this month Viveve announced 12-month results of its feasibility study evaluating their Viveve System technology for the treatment of women with mild-to-moderate stress urinary incontinence (SUI). The following week, results were presented at a SUI-focused KOL symposium sponsored by the company. The data, we believe, largely confirms the compelling efficacy signal seen at six months, which was announced in June. And while it appears, as might be expected, that there was somewhat of a deterioration of effectiveness from the six-month to the twelve-month follow up, with results of the 1-hour pad weight test continuing to show substantial improvement from baseline, we think this latest data further bolsters the likelihood of eventual success of the pivotal LIBERATE SUI studies.
In mid-June Viveve announced what we characterized as potentially compelling 6-month data from its SUI 12-month feasibility study. Results at six-months and our accompanying commentary are available in our Appendix (see link to our full report). And, for ease of reference, we have also included them in our 12-month results table below.
At the time of the 6-month data release we noted that while given that this was a small single-arm study with data only through 6 months, we could not draw concrete conclusions in terms of efficacy. But, we also noted that combined with positive data of the prior n=10 pilot study, results certainly appeared to support the hypothesis that the Viveve system may have real clinical utility in improving SUI symptoms. Further, we explained that from a regulatory standpoint, efficacy through 12 months is what is important – we expected to know a lot more in terms of the potential utility of the Viveve system in SUI when 12-month results of this study were available.
Results: 72% Experience Reduction in Pad Weight Resulting in 56% Mean Reduction. Response Particularly Strong in More Severe SUI
While intended enrollment was 36, 28 patients completed follow-up through six months and 25 through 12 months. On a side note, this ~30% drop out rate may actually be quite indicative of some of the difficulty in effectively treating SUI with non-surgical therapy such as pelvic floor muscle exercises. Specifically, non-compliance (due to busy lives or other reasons) results in less effective outcomes. It is also suggestive of some of the potential appeal of Viveve SUI therapy – that is, a single, non-invasive treatment does not require rigid compliance (which is in addition to the benefits to surgical options).
– 1-hour pad weight test: this is the primary endpoint in LIBERATE International (through six months) and is expected to also serve as the primary endpoint in LIBERATE U.S. (through 12 months). As measured by the 1-hour pad weight test, average aggregate urine leakage decreased by 56% from baseline (7.3g vs 3.2g) and 72% (18 of 25) of women experienced improvement.
For reference, FDA recommends (for the design of pivotal SUI studies) defining ‘clinically meaningful improvement’ as a reduction in urine leakage of 50% or more. On this measure, 52% of all patients showed a clinically meaningful improvement. And perhaps even more compelling, is that 67% of those patients (n=10) diagnosed as having moderate (that is, more severe) SUI, had a clinically meaningful reduction in leakage. Additionally (as it relates to the 1-hour pad weight test), 60% and 50% of all women and women with moderate SUI, respectively, met the clinically meaningful definition of ‘dryness’ – which is defined as urine leakage of one gram or less.
Given the particularly robust effectiveness in ‘moderate’ SUI patients, VIVE expects to power their U.S. LIBERATE study with similarly diagnosed severity – which should further enhance the chances of success of that study – which would further enhance eventual likelihood of U.S. label expansion for SUI.
– Secondary endpoints: while detailed results of the PRO secondary endpoints were not discussed in detail, Viveve noted in the data release that clinically meaningful benefit was achieved at 12 months across all patient reported outcome measures. The results are also included in the table below.
View Exhibit I
We think this data affirms the efficacy signal witnessed through six months and further bolsters the likelihood of eventual success of both LIBERATE studies. During the KOL symposium presentation management also provided updates relative to VIVIVE II, LIBERATE International and LIBERATE U.S.
As it relates to the LIBERATE studies….
In August VIVE announced commencement LIBERATE-International, which (if successful) is expected to be used as primary support for SUI regulatory filings seeking marketing clearance in Canada and Europe. To-date, ~76 patients (of 99 total) have been enrolled across eight active sites. Another 19 have been screened and enrollment could complete within the next few weeks. Management is currently estimating that full results could be available in Q3 2019 (slightly delayed from prior ~mid-2019 expectation).
Meanwhile, in September VIVE made an IDE filing seeking approval to commence its U.S. SUI pivotal study, LIBERATE-U.S. While the hope had been that LIBERATE-U.S. could begin by late-2018/early-2019, that looks like it will not happen. During the SUI KOL symposium presentation management noted that, after a couple of rounds of questions from FDA regarding VIVE’s IDE application, the agency requested that the company conduct a sheep safety study. VIVE further noted that this is very similar to what was required of them for final support of their VIVEVE IDE – which was eventually approved.
Given the demonstrated safety to-date in SUI (including acceptable safety/tolerability in the latest 12-month results) as well as in sexual function/vaginal laxity indications, coupled with the fact that this sheep study may effectively be a repeat of what was just successfully conducted, we have little concern that this will be problematic towards eventual IDE approval. But, it does push back anticipated timelines for LIBERATE U.S. Management hopes to have the sheep study completed in 1H’19. They will then need to file an IDE supplement and, if all goes well, be in a position to start LIBERATE U.S. in the back half of next year. If that happens, management thinks they could have full 12-month data in late-2020/early-2021.
We are already anxiously awaiting data from LIBERATE – and particularly from the U.S. study – which we do think is likely to successfully navigate the IDE process. If this recent compelling 12-month feasibility study data can be replicated (or at least strongly supported) in a pivotal U.S. study, we think it could be a substantial value inflection event for VIVE. The relatively massive size of the SUI market (~30M women) and current lack of effective, non-invasive and affordable treatment options means adoption of Viveve treatment in this indication could be quite rapid and potentially dwarf that of use for vaginal laxity/sexual function.
VIVEVE II Update
As a reminder, VIVE received IDE approval of VIVEVE II in March 2018 and in mid-May announced that the study had started. VIVEVE II, if successful, is expected to provide the backbone for an eventual U.S. regulatory filing seeking an indication for ‘treatment of sexual function’.
VIVEVE II is using a ‘staged roll-in’ enrollment approach which is further aimed at ensuring safety. While total enrollment is expected to be 250, this staged roll-in requirement means a safety review must be conducted on the initial patients before additional subjects can enter the study. In early August VIVE announced that, following one-month safety review of the first 25 patients, that FDA approved enrollment to continue up to 100 (i.e. second stage). FDA did another safety review once another 25 patients had been followed for one-month and 3-month data was available on a total of 50 patients. Management noted on the Q3 call (in November) that they expected to file this safety data, accompanied with an IDE application requesting to enroll the remaining 150 patients, by the end of November.
Apparently that happened as Viveve announced on December 20th that FDA approved enrollment to continue through to the total of 250. This approval was important given that it was a gatekeeper to finishing the study but, as we noted in our prior update, we think it may also play a role in re-accelerating domestic sales growth given that it is further evidence supporting the safety of Viveve treatment. If so, it is possible that FDA’s green-lighting of the final enrollment cohort to proceed could resonate with potential purchasers of the system that may have been hesitant to do so due to the unfortunate halo effect of FDA’s warning letter.
Management noted during the SUI KOL symposium that 19 sites are currently actively enrolling and now expects that final results of VIVEVE II could be available sometime in Q1 2020 (largely unchanged from prior expectations).
VIVE beefed up their cash position through the recent sale of 13.3M common shares at $1.50/share for gross and net proceeds of $20.0M and ~$18.8M, respectively. With average quarterly operating burn of ~$11M and $20M cash on the balance sheet as of the close of Q3, we estimate current cash position is ~$30M. We think this should be sufficient to fund operations through at least mid-2019 and quite possibly through Q3 of next year.
DISCLOSURE: Zacks SCR has received compensation from the issuer directly or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks provides and Zacks receives quarterly payments totaling a maximum fee of $30,000 annually for these services. Full Disclaimer HERE.